Journal
ANTIVIRAL RESEARCH
Volume 96, Issue 2, Pages 213-220Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2012.09.009
Keywords
Foot-and-mouth disease virus; Antiviral agent; Interferon; Small interfernce RNA; Ribavirin; Combination
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Funding
- Animal, Plant and Fisheries Quarantine and Inspection Agency (QIA), Republic of Korea
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Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. The current FMD vaccine provides no protection until 7 days after the vaccination, which reduces its effectiveness in the case of an outbreak. Therefore, to find an alternative method of applying antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we compared the antiviral effects of promising antiviral agents and attempted to apply them in combination. First, we measured and compared the 50% effective concentration (EC50) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC50) to the mean cytotoxicity of antiviral agents such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or porcine interferon-a (Ad-porcine IFN-alpha) in swine kidney cells (IBRS-2). The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad-porcine IFN-a were 7 x 10(3) or 7 x 10(4) based on the adenoviral titer. Next, we tested the combined effects of the FMDV inhibition agents. Enhanced inhibition effects were observed in the IBRS-2 cells and in suckling mice from the combination of Ad-porcine IFN-alpha and Ad-siRNA or ribavirin. The combined application of these recombinant adenoviruses and ribavirin may enhance their inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents. (C) Elsevier BM. All rights reserved.
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